Behavioral & Pharmacological Analysis of Drugs of Abuse

50多年前，艾伯特·霍夫曼发现了LSD的致幻作用，这一发现不可逆转地改变了生物精神病学和流行文化的进程。在这个国家，所有类型的致幻剂都受到青少年和年轻成年人广泛和日益增加的滥用。例如，1998年，在12-17岁和18-25岁年龄组中，致幻剂的使用量超过了可卡因。事实上，致幻剂比镇定剂、吸入剂和镇静剂加起来更常被摄入。此外，1999年，在国家药物滥用研究所的运动中，LSD被确定为“俱乐部毒品”，以提醒公众注意这些药物的危害。除了公认的这些药物的滥用责任外，致幻剂也许是独特的，因为了解它们的作用机制不仅有助于减轻非法使用的负担，而且还可能为解决精神病这一人类的另一主要痛苦难题提供钥匙。目前的研究试图在行为、生化和分析[GC-MS]联合研究中表征吲哚胺致幻剂，如LSD和苯乙胺致幻剂。具体地说，研究还将检查与致幻剂诱导的刺激控制有关的神经解剖学部位。此外，实验将进一步表征大脑中血清素能和谷氨酸能系统之间的相互作用。最后，将探讨氟西汀和相关的选择性血清素再摄取抑制剂对LSD和其他致幻剂的增强作用机制。综上所述，对体内和体外功效以及DOM和神经递质的脑水平进行评估的有力方法的相关使用将为致幻剂的作用方式提供新的认识。

The discovery by Albert Hofmann more than fifty years ago of the hallucinogenic effects of LSD irreversibly altered the course of both biological psychiatry and popular culture. Hallucinogens of all types are subject to widespread and increasing abuse by adolescents and young adults in this country. For example, in 1998 use of hallucinogens exceeded that of cocaine in the age groups 12-17 and 18-25. Indeed, hallucinogens were more commonly ingested than tranquilizers, inhalants, and sedatives combined. Furthermore, LSD was identified in 1999 as a "club drug" in the campaign by the National Institute on Drug Abuse to alert the public to the hazards of these agents. In addition to the well recognized abuse liability of these drugs, hallucinogens are perhaps unique in that an understanding of their mechanisms of action would contribute not only to an amelioration of the burdens of illicit use but might also provide a key to solving the puzzle of psychosis, another major human affliction. The present investigations seek to characterize indoleamine hallucinogens such as LSD and phenethylamine hallucinogens as exemplified by DOM in combined behavioral, biochemical, and analytical [GC-MS] studies. Specifically, studies will also examine the neuroanatomical sites involved in hallucinogen- induced stimulus control. In addition, experiments will further characterize interactions between the serotonergic and glutamatergic systems in the brain. Finally, the mechanisms responsible for the potentiation of LSD and other hallucinogens by fluoxetine and related selective serotonin reuptake inhibitors will be examined. Taken together, the correlational use of powerful methods for the assessment of in vivo and in vitro efficacy and of brain levels of DOM and of neurotransmitters will provide new understanding of the mode of action of hallucinogens.